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Lisa A. Carey, MD; Charles M. Perou, PhD; Chad A. Livasy, MD; Lynn G. Dressler, PhD; David Cowan, BS; Kathleen Conway, PhD; Gamze Karaca, MSc; Melissa A. Troester, PhD; Chiu Kit Tse, MSPH; Sharon Edmiston, BS; Sandra L. Deming, PhD, MPH; Joseph Geradts, MD; Maggie C. U. Cheang, MMedSci; Torsten O. Nielsen, MD; Patricia G. Moorman, PhD; H. Shelton Earp, MD; Robert C. Millikan, DVM, PhD

JAMA. 2006;295:2492-2502.

Context  Gene expression analysis has identified several breast cancer subtypes, including basal-like, human epidermal growth factor receptor-2 positive/estrogen receptor negative (HER2+/ER–), luminal A, and luminal B.

Objectives  To determine population-based distributions and clinical associations for breast cancer subtypes.

Design, Setting, and Participants  Immunohistochemical surrogates for each subtype were applied to 496 incident cases of invasive breast cancer from the Carolina Breast Cancer Study (ascertained between May 1993 and December 1996), a population-based, case-control study that oversampled premenopausal and African American women. Subtype definitions were as follows: luminal A (ER+ and/or progesterone receptor positive [PR+], HER2–), luminal B (ER+ and/or PR+, HER2+), basal-like (ER–, PR–, HER2–, cytokeratin 5/6 positive, and/or HER1+), HER2+/ER– (ER–, PR–, and HER2+), and unclassified (negative for all 5 markers).

Main Outcome Measures  We examined the prevalence of breast cancer subtypes within racial and menopausal subsets and determined their associations with tumor size, axillary nodal status, mitotic index, nuclear pleomorphism, combined grade, p53 mutation status, and breast cancer–specific survival.

Results  The basal-like breast cancer subtype was more prevalent among premenopausal African American women (39%) compared with postmenopausal African American women (14%) and non–African American women (16%) of any age (P<.001), whereas the luminal A subtype was less prevalent (36% vs 59% and 54%, respectively). The HER2+/ER– subtype did not vary with race or menopausal status (6%-9%). Compared with luminal A, basal-like tumors had more TP53 mutations (44% vs 15%, P<.001), higher mitotic index (odds ratio [OR], 11.0; 95% confidence interval [CI], 5.6-21.7), more marked nuclear pleomorphism (OR, 9.7; 95% CI, 5.3-18.0), and higher combined grade (OR, 8.3; 95% CI, 4.4-15.6). Breast cancer–specific survival differed by subtype (P<.001), with shortest survival among HER2+/ER– and basal-like subtypes.

Conclusions  Basal-like breast tumors occurred at a higher prevalence among premenopausal African American patients compared with postmenopausal African American and non–African American patients in this population-based study. A higher prevalence of basal-like breast tumors and a lower prevalence of luminal A tumors could contribute to the poor prognosis of young African American women with breast cancer.

Author Affiliations: Division of Hematology/Oncology (Dr Carey), Departments of Medicine (Drs Dressler and Earp and Mr Cowan), Genetics (Dr Perou and Ms Karaca), and Pathology (Drs Perou and Livasy), School of Public Health, Department of Epidemiology (Drs Conway, Troester, Deming, and Millikan and Mss Tse and Edmiston), University of North Carolina-Lineberger Comprehensive Cancer Center, Chapel Hill; Department of Community and Family Medicine, Duke University Medical Center, Durham, NC (Dr Moorman); Genetic Pathology Evaluation Centre, University of British Columbia, Vancouver (Dr Nielsen and Ms Cheang); and Roswell Park Cancer Institute, Buffalo, NY (Dr Geradts).

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